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Tuesday, July 30, 2013

Penn State was recently awarded the NIH predoctoral (T32) training grant: Computation, Bioinformatics and Statistics (CBIOS) Training Program, led by Ross Hardison, Debashis Ghosh, and Cooduvalli Shashikant. They are now seeking to recruit talented students, and are specially seeking students interested in cross-disciplinary research. To be eligible for the training program, one should be admitted to one of the six participating graduate programs including IBIOS-BG (the option where I did my PhD!!), with emphasis on individuals from underrepresented groups, and US citizens. The first year students apply to the program in the fall semester and begin training in spring semester. They will be supported for two years from CBIOS funding.

I thoroughly enjoyed my time as a graduate student in the Bioinformatics and Genomics (BG) option, and highly recommend it to any undergraduates considering graduate school. Penn State has excellent research programs and brilliant faculty, but that isn't enough. What set Penn State apart was how inclusive an environment it was. As a graduate student I felt like my opinions and ideas were valued. The culture at Penn State encouraged me to learn from my mistakes, and to comfortable admitting when I didn't know something. I was encouraged to be proactive in my training, coursework, and planning my own research.

If you are (or know of) a stellar undergraduate interested in studying bioinformatics, please apply (or encourage them to apply) to this program.

Now, take a look at this winning poster from a team of Penn State researchers entitled, "Powering Your Car with Sunlight"! The researchers were allowed one word in addition to the list of 1000 common words: energy.

Read more about their effort here, and check out the other poster entries here.

Yes, we can more efficiently explain our research when we use language that is more technical than the 1000 most common words. But I will argue that we can more effectively communicate our research when we take the time to consider the minimal level of technical jargon needed to convey the underlying principles.

Saturday, July 27, 2013

We are just finished two weeks without daycare (the family daycare that we go to closes for two weeks in the summer and two weeks in the winter of paid vacation). The husband and I are lucky to both be postdocs with flexible schedules, and understanding advisers. Also, being the summer, and right after a conference, it is pretty quiet in my lab. Even though I'm in a cubicle office with 12-16 other spaces, during the past two weeks there have only been a handful of us in the office. So, Little Bear has come in with a couple days.

Seriously, this is adorable.

We've been trading off, and working both evenings and weekends. For me this has amounted to roughly 6 hours every day, for about 40ish hours of work each week. Granted, that's not considered "full-time" in academia, but it has been enough for me to make small steps. Most of the time I've had in lab has been spent meeting with my undergraduate students, while most of the time at home has been writing and catching up on the current literature.

Let me tell you, being able to work part time, and be home part time with Little Bear was incredible.

We've worked on potty training, gone to the library, the park, the YMCA, played monsters, painted, danced, cooked, ran errands, and snuggled. Sure, I get to do all of these things, in limited quantity, in the evenings and on weekends, but it feels so rushed. You should also know that a constant frustration of mine is that nearly all of the organized
"kid-friendly" activities during the week are not generally "working-parent-friendly" because they are planned for the middle of the traditional work day. That means people like me necessarily miss them all
during the week (e.g., story hour at the library and toddler swim at the
YMCA). The last two weeks I still had the time to wear my academic hat, which felt a little stressful given the reduced time. But, the extra hours during the day meant that I could truly take advantage of some of the kid-friendly activities around town.

After these two weeks I feel refreshed, and even a little antsy to get back into research full time. I feel reinvigorated, and ready to jump into writing. I feel super excited that we've gone five full days without an accident. Well, no accidents for the Little Bear. Seriously, I've never been so excited about pee and poop in the potty. Maybe I should get into microbiome research.

Now, on Saturday night, the Little Bear is sleeping soundly, and I'm thinking about our last two weeks. As excited as I am to get back into work (and I truly am), I am so sad all over again to send her to daycare on Monday. I am comforted by how much she loves it there, and how much they love her. I know she is happy and healthy and growing. But I miss her so much. I miss her already. It crushes my heart.

In the shadow of preparing job materials, this feeling makes me realize that I need to work hard to find a career that works for me.

This smile is worth more than any grant.

Let me take a minute to pause and recognize that I understand how fortunate I am to be at a place in my life where I can consider what kind of career I want to make me happy.

But here is where I am, and I need to decide what kind of environment will be best for me, the whole me, and for my family. This, brashly, assumes that after all my applications I'll get some interviews and be offered any positions. So, wish me luck.

Thursday, July 25, 2013

I'm working on an article discussing "Trends in Evolution", to be written for a broad audience interested in science, but not experts. I've already narrowed it down to a few sub-topics to focus on, but I would like some advice on figures.

I am working on figures to succinctly illustrate how evolution works, while also addressing common misconceptions. What do you think? How can I improve these? What have I unwittingly misrepresented? Which do you like best?

1. Evolution is the gradual change of populations over time, not distinct transitions between species.

Here, I've already received feedback that I should remove the word "gradual". I agree that "gradual" is a relative term, and in many cases, evolution happens very quickly. Given that I work on long-lived species, I tend to use "gradual", and like it for this example.

Tuesday, July 23, 2013

Sex chromosomes are fascinating, and we still have so much to learn about how they originate and change over time. This last week I had the pleasure of talking to one of the leaders in the field,
Deborah Charlesworth, about explaining sex chromosome evolution and
genetics. I hope she'll forgive me for this simplification of a
recent beautiful genetic analysis from her lab.

I study sex chromosomes in mammals (X and Y), but lots of other wonderful species have evolved chromosomal sex determination (instead of, say, using temperature or environmental cues to determine males and females).

One of those species is a lovely plant called Silene latifolia, also called a White Campion.

The plant, Silene latifolia, with sex chromosomes

This plant has very young sex chromosomes. Whereas the sex chromosomes in mammals look very different from each other (the X is large and full of genes, while the Y is small and gene-poor), the X and Y chromosomes of the Silene latifolia look more similar to each other. Moreover, while there is good evidence that the mammalian sex chromosomes started to differentiate from one another about 160 million years ago, the X and Y of Silene latifolia only started differentiating from one another 10-20 million years ago. This time can be estimated by comparing the number of differences between genes with one partner on the X and one partner on the Y (the longer the time since they started differentiating, the more differences will have accumulated between the once-identical X and Y sequences), and also by identifying which closely-related species have (or do not have) the same sex chromosome system. The very young sex chromosomes in Silene latifolia are exciting because they let us look at some of the changes that occur during the very early stages of sex chromosome evolution.

Bergero et al. (2013) studied the sex chromosomes of Silene latifolia, and compared those regions with a closely-related species without sex chromosomes (Silene vulgaris, the ugly stepsister-species), to learn about some

Just a quick reminder. The autosomes (non-sex chromosomes) can swap DNA anywhere. Most sex chromosomes, especially young sex chromosomes have a region that still swaps bits of DNA between the X and Y - this is called the pseudo-autosomal region, or PAR. The rest of the sex chromosomes, the sex-specific regions, cannot swap bits of DNA.

Bergero et al. (2013) did a lot of molecular genetics to better understand the sex-specific and the pseudoautosomal regions of the beautiful S. latifolia sex chromosomes. They found:

1. Single ancient source of the original S. latifolia X chromosome.
First, Bergero et al. (2013) found that the genes in the sex-specific regions are found in a single location in the sister species, suggesting that this sex-specific region evolved from a single ancestral autosomal ancestor (green blocks).

Like many sex chromosomes, the S. latifolia sex chromosomes have a sex-specific region and a pseudoautosomal region (not sex-specific).

2. Two independent additions to the S. latifolia X chromosome.
Looking at the pseudoautosomal region (PAR), Bergero et al. (2013) found that the genes in the S. latifolia PAR are found to reside in two unique regions on the autosomes in the sister species. Moreover, both of these sets of PAR genes are found in a different location from where the sex-specific genes cluster, suggesting they were added at different times (first the block of blue genes, and second the block of red genes).

There appears to have also been some rearrangement of the genes in the red and blue regions, but for simplicity, I'll keep them as blocks here.

3. X-Y differentiation is still very active.

Lastly, even though the additions (blue and red) were recent, Bergero et al. (2013) found some evidence that a portion of the additional blocks of genes that have a few unique X-variants and a few unique Y-variants, suggesting that the X-Y swapping stopped recently, or is in the process of stopping. This means that these regions are just now accumulating differences between the X and Y.

Sex chromosomes (some even younger than S. latifolia) exist in many other plants (e.g. papaya and strawberry). These systems let us learn how quickly sex chromosomes can evolve, and can shed light on how our own, old, sex chromosomes change over time.

And in that moment it suddenly dawned on me what was taking me down. We (myself included) admire the obsessively dedicated. At work we hail the person for whom science and teaching is above all else, who forgets to eat and drink while working feverously on getting the right answer, who is always there to have dinner and discussion with eager undergrads. At home we admire the parent who sacrificed everything for the sake of a better life for their children, even at great personal expense. The best scientists. The best parents. Anything less is not giving it your best.

And then I had an even more depressing epiphany. That in such a world I was destined to suck at both.

Needless to say it took a lot of time, and a lot of tears, for me to dig myself out of that hole. And when I finally did, it came in the form of another epiphany. That what I can do, is try to be the best whole person that I can be. And that is *not* a compromise. That *is* me giving it my very best. I’m pretty sure that the best scientists by the above definition are not in the running for most dedicated parent or most supportive spouse, and vice versa. And I’m not interested in either of those one-sided lives. I am obsessively dedicated to being the best whole person I can be. It is possible that my best whole is not good enough for Harvard, or for my marriage; I have to accept that both may choose to find someone else who is a better fit. But even if I don’t rank amongst the best junior faculty list, or the best spouses list, I am sure there is a place in the world where I can bring value.

You know what I think my job is? Respond to life as it happens. Stop expecting balance.

Wake up. See what needs to be done right now. Let go of the idea that my life should carry on in some neat, systematic way and that someday I’ll be meeting all the needs of all the people all the time.

As if someday my marriage will be totally equal all the time and my health will be solid (cause I’m exercising and eating a balanced diet) and my kids are thriving neatly (just as they should!) and my house is put together (but not too put together because one must not obsess) and I’ll go to work and “Leave it there” when I leave (cause one shouldn’t bring that stress home) and I’ll take my “me time” with my friends and husband (because mental health, people!).

Or I’ll realize shit like that only happens in movies and self-help books.

Today I had one of those wonderfully "normal" and busy days that I feel jealous of whenever I see my stay-at-home mom friends' statuses. Today's activities included doing laundry and grocery shopping with the family, cleaning the house, making carrot cake granola bars and painting with the Little Bear, actually making breakfast (egg bagel sandwiches), lunch (roasted eggplant and zucchini pasta) and dinner (tofu, rice and premade saag panner), having family bubble blowing time, bathing Little Bear and then having her help me bathe Little Brown Dog, then reading stories and singing bedtime songs.
And then it came time to get to work, and I just... I couldn't. Luckily, I had the wonderful reading above.

Saturday, July 20, 2013

During the week we usually have a quick breakfast like scrambled eggs, oatmeal, granola bars, or cereal. On the weekends, however, we try for something more fun, like paleontology pancakes. I keep testing different recipes with greater or lesser success, but the really important part is the consistency so that I can get a good shape out of them.

Pteranodon with speckled eggs

Inspecting breakfast.

T-rex is pretty difficult, because of its tiny arms, but pteranodon, stegosaurus, and apatosaurus come out at least somewhat resembling what I intended.

Pancakes are something that are fun to make together. I really enjoy letting Little Bear help me out in the kitchen. I sit her down, measure things out, and let her do the dumping and stirring. It has also been a nice tool for teaching her how to be careful around the oven and stove. If everything is going really well, she'll even help set the table.

I am constantly amazed by how much she can do if I just give her the opportunity to try (and fail). I'm trying to remember this lesson with my students as well.

Tuesday, July 16, 2013

Daniel Wegmann: Every non-lethal genome position is variable in the human population #bc2
— Tuuli Lappalainen (@tuuliel) July 4, 2013

Really?

There are 23 pairs of chromosomes in the human genome. If you counted the number of positions - A's, T's, G's, and C's - you would have approximately three billion positions across those 23 chromosomes. And because each chromosome is part of a pair, you can multiply that number by two, for a total of six billion places where a mutation can happen. Assuming there are not very many lethal positions, is it really possible to have a mutation at every site in at least one living human?

Yes!

In fact, we expect that across all humans, there are over 100 mutations at every single position in the human genome. And, here is the math to prove it:

The average mutation rate in the human genome is 1.2 x10^-8 mutations per site per generation. This is pretty small, so in each person, we only expect to observe a handful of new mutations relative to their parents. But, that handful of mutations adds up when you think of how many people are on the earth.

There are now 7.16 billion people on earth (at the time of this post the estimate was 7,165,212,612 ish).

If we let the birth of every person alive represent a single generation event, then we can estimate the average number of new mutations at each site across all 7.16 billion people by multiplying the mutation rate per generation, by the number of generations:

This says that if we could look at the genome of all 7 billion people, on average, we expect to observe 86 new mutations at each of the six billion individual positions across the genome. But we usually don't talk about each copy of a chromosome individually (the one you got from your mother and the one you got from your father), we just talk about a single chromosome, like chromosome 1. That is, we think about the genome as folded in half (that three billion number I first mentioned).

So, the folded number (thinking about the number of differences across the three billion sites), suggests that there are about 172 mutations at each site of every chromosome across the whole human population.

That sounds like a lot of mutations, and it really is, but think about all of the people on the earth!

A beach in Sri Lanka, by Denish C

Taipei Rapid Transit on New Year's Eve, by Changlc

School dedication ceremony, Pongwe, Tanzania, by Jesse Awalt

Urawa Reds vs Gamba Osaka in Tokyo, Japan, by Pocopen

When we consider all 7 billion of us together, a little math shows that, even though there are only a small number of new mutations in each individual, there really can be mutations at every single position in the genome. In fact, we expect hundreds of mutations at every single (non-lethal*) site!

Wow!!

*A mutation that results in death would not be tolerated, so we would not expect to observe mutations at a select set of very important sites. BUT, a mutation that is harmful in one tissue (like the brain) may not have any effect in a different tissue (say, the skin). That is a story for another day.

Monday, July 1, 2013

Many times we utilize and study the products of evolution that result from species sharing a common history. For example, the reason we can use mice for studies of human diseases and medical treatments is that, because of shared ancestry, a mouse body and the set of mouse genes is similar enough to a human body and the set of human genes that both will develop similar diseases, and respond similarly to treatments.

There are other products of evolution that occurred independently, and are not the product of common ancestry. This is more likely to happen if a feature is useful in certain environments, but wasn't present in the common ancestor. For example, although a shark is a fish, and a dolphin is a mammal, both evolved sleek fins for gliding through the water (one of the many clues that they do not share a common ancestor is that the shark skeleton, like other fish, is structured so that a shark tail swims left to right, but a dolphin's skeleton is structured like that of other mammals, and as a result the dolphin tail swims up and down).

Just as we can take advantage of shared evolutionary history to learn more about ourselves, we can also study cases of convergent evolution to learn more about, well, ourselves!

For example, eyes evolved multiple times throughout the evolutionary tree. Specifically, the eyes of squids evolved independently of ours, but function in very similar ways. Because of the similar function, squid eyes can be affected by disorders, like myopia (being near-sighted/short-sighted), that affect human eyes. By studying how the squid eye evolved, and how it develops now, scientists hope to make advances in understanding and treating eye disorders in humans. Emma Goodman put together a wonderful summary of this, "Eyevolution":

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